We propose four interrelated subprojects to define the biomechanics of the eye rotating (extraocular) muscles (EOMs) and other tissues in health and disease, understand novel EOM actions, and characterize effects of nerve damage to EOMs. This effort is to improve diagnosis and surgical treatment of strabismus, which is misalignment of the directions of the two eyes. Aim I will clarify the role of connective tissue degeneration in common forms of strabismus that develop in adults, testing the hypothesis that some forms of acquired horizontal or vertical double vision are caused, not by brain or nerve disease as widely supposed now, but instead by connective tissue degeneration that alters EOM paths. Such degeneration would not signify neurological disease but may be corrected by surgery. Aim II will characterize effects of nerve damage on EOMs in common clinical strabismus syndromes treated by EOM surgery, including palsy of the trochlear, oculomotor, and abducens nerves, to clarify the time course and extent of mechanical changes such as EOM thinning and stretching, and possibly regrowth of damaged nerves or substitution by other nerves. Parallel studies will validate magnetic resonance imaging (MRI) of the eye sockets by comparison with microscopic changes to improve diagnostic specificity. Aim III will test a new hypothesis that nerve control selective for individual parts of EOMs permits them to have important mechanical actions not currently considered in their physiological repertoire, and hence confounding to clinicians who treat strabismus. Microscopic studies of intramuscular nerve distributions will be complemented by functional studies using structural and motion encoded MRI during binocular gaze changes, convergence to near targets, and head tilting to determine the influence of selective EOM actions on binocular alignment. Aim IV will characterize and model behavior of orbital fibromuscular tissues, using the modern mechanical engineering technique of finite element analysis (FEA) to integrate data on EOM and connective tissue properties obtained using novel techniques of minimal indentation, and dual-mode loading at lifelike speed and acceleration. Biomechanical testing will test the potential for selective compartmental action in EOMs. FEA based on accurate biomechanical data will be compared using 3-dimensional computer visualization with pre- and post-operative MRI to understand and improve surgical treatment of double vision caused by connective tissue degeneration. PUBLIC HEALTH RELEVANCE: Strabismus is a common clinical disorder in which misalignment of the eyes can cause double vision in adults, and visual loss in children. Strabismus is often treated by surgical manipulation of mechanical properties of muscles and connective tissues in the eye socket. Improved understanding of mechanical properties and nerve control of eye socket tissues will improve the diagnosis of eye and brain diseases, and enhance the success of strabismus surgery.